by Multiple sclerosis (MS) is a chronic inflammatory disease that attacks the protective myelin sheath surrounding the nerve fibers of the central nervous system. When the myelin sheath is damaged, nerve impulses travelling to and from the brain and spinal cord are disrupted, leading to a wide range of symptoms. MS typically affects adults between the ages of 20-50 and is more common in women than men. While the exact cause remains unknown, it is believed to be an autoimmune disorder where the immune system mistakes myelin for a foreign substance and attacks it.
First-Line Disease-Modifying Multiple Sclerosis Therapeutics
The Multiple Sclerosis Therapeutics therapies (DMTs) for relapsing forms of MS aim to reduce frequency and severity of relapses and slow progression of disability. Interferon beta-1a and 1b were among the first DMTs approved in the 1990s for MS. These injectable drugs work to modulate the immune system and reduce inflammation. Common side effects include flu-like symptoms. Glatiramer acetate is another first-line DMT administered via daily subcutaneous injections. It works similarly to interferons and has a good overall safety profile. Oral drugs have since emerged as more convenient options. Fingolimod was the first oral therapy approved in 2010 and works by preventing lymphocytes from leaving lymph nodes, thus reducing their activity in the central nervous system. It has shown benefits in reducing relapses and disability progression but requires cardiac monitoring. Dimethyl fumarate and teriflunomide are other oral options that are generally well-tolerated.
Specially-Dosed Antineoplastic Therapies
For patients with highly active relapsing-remitting MS (RRMS), antineoplastic therapies originally approved for cancer indications have emerged as more potent treatment options. Natalizumab (Tysabri) is delivered via monthly intravenous infusions. It is very effective at reducing relapses but carries an increased risk of progressive multifocal leukoencephalopathy (PML), a rare brain infection caused by the JC virus. As a result, it is generally reserved for patients with very active disease who have failed other therapies. Mitoxantrone is approved for secondary progressive MS (SPMS) and aggressive RRMS. Given by quarterly intravenous infusions for a maximum of 2 years, it suppresses immune activity but has potential heart and cancer risks with long-term use. Ocrelizumab (Ocrevus) was the first drug approved in 2017 for both RRMS and primary progressive MS (PPMS). Given by 6 monthly intravenous infusions, it selectively targets B cells to reduce inflammation. Infusion reactions are possible with first doses.
Relapse Management and Symptomatic Therapy
For managing MS relapses, corticosteroids such as methylprednisolone are commonly prescribed as they can help speed recovery. Symptomatic therapies do not affect disease progression but target specific MS symptoms. Bladder and bowel dysfunction is treated with medications such as oxybutynin and tolterodine. Muscle spasticity is managed with baclofen, tizanidine or botulinum toxin injections. Pain is treated with gabapentinoids and tricyclic antidepressants. Fatigue is somewhat alleviated with immunomodulatory therapies but amantadine and modafinil may provide additional benefit.
Emerging Therapies
Many new DMTs in late stages of development aim to provide better efficacy, safety, route of administration or target additional disease mechanisms compared to current options. Siponimod is an oral sphingosine 1-phosphate receptor modulator that may reduce relapse rates and disability progression similarly to injectable therapies. Cladribine is an older chemotherapy drug being repurposed orally for MS and has shown potential as an annual or biennial treatment. Ofatumumab targets a distinct epitope on B cells compared to ocrelizumab and is delivered subcutaneously. Other B cell depleting therapies include evobrutinib, unifumarin and tamiralizumab. Anti-CD20 therapies such as ublituximab combine immune effects with favourable safety profiles. Alpha-4 integrin receptor antibodies such as etrolizumab could benefit patients intolerant or partially-responsive to natalizumab. Additional drug classes in late stages of MS research are tau antibodies, complement inhibitors, remyelination promoters and neuroprotective agents.
Current disease-modifying and symptomatic therapies have significantly improved quality of life for many MS patients by decreasing relapses, prolonging time between attacks and managing symptoms. However, further advancements are still needed to achieve full prevention of disability accumulation and neurodegeneration across all MS subtypes. Continued research into additional immunomodulatory, neuroregenerative, and neuroprotective approaches holds promise for developing even more effective treatments with improved safety profiles in the future. With the successful approval and adoption of new therapies, options for personalized management of MS will continue expanding based on individual disease characteristics and drug response.
*Note:
1.Source: Coherent Market Insights, Public sources, Desk research
2.We have leveraged AI tools to mine information and compile it
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